tbuckley/cabot-search huggingface dataset:
Rates of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) from Center for International Blood and Marrow Transplant Research (CIBMTR) data on US subjects (SUBJ) with lymphoma following chimeric antigen receptor T cell therapy (CAR-T).
Authors: Matthew J. Frigault, Theresa Amoloja, Lea Micaletti Burke, Rodica Morariu-Zamfir, Valkal Bhatt, Kristen Bibeau, Xiao Ying Tang, Amy Moskop, Richard T. Maziarz, John F. DiPersio
Journal: Journal of Clinical Oncology (2023)

7528 Background: The engineered T-cell products axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are FDA approved for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), respectively. This study investigated real-world rates of CRS and ICANS following CAR-T. Methods: This study analyzed CIBMTR data of US SUBJ receiving axi-cel or brexu-cel for any indication from Oct 2020–Dec 2021 with ≥1 follow-up visit. CRS and ICANS were graded per American Society for Transplantation and Cellular Therapy consensus guidelines. Results: 927 SUBJ (median age, 63 y; men, 65%) from 87 centers were analyzed. Most received axi-cel (76%), 83% of whom had DLBCL or transformed follicular lymphoma (tFL); 24% received brexu-cel (MCL). Most SUBJ had Ann Arbor stage III/IV (63%), no active central nervous system disease (84%), and refractory disease at CAR-T infusion (66%). Among all 589 SUBJ with DLBCL/tFL who received axi-cel, 54% achieved complete response, 17% partial response, and 6% stable disease. 89/715 SUBJ with available data received treatment for CRS prevention, mostly tocilizumab alone (80% [71/89]) or in combination (3% [3/89]). Overall, 766 SUBJ (83%) developed CRS (grade ≥3, 64 [8%]; Table). Of the 89 SUBJ who received CRS prevention treatment, 78% developed CRS, with 3% (3/89) having grade ≥3. 77% of SUBJ with CRS received CRS treatment, 97% of whom received tocilizumab (alone or in combination [eg, with corticosteroids]). Most (64%) SUBJ with grade 1 CRS received treatment, 63% of whom received tocilizumab alone. ICANS occurred in 424/876 SUBJ with ICANS data (48%; Table), of whom 205 (48%) had grade ≥3. ICANS treatment was reported and administered to 86% of SUBJ with ICANS, 92% of whom received corticosteroids. Conclusions: CRS and ICANS incidence rates were consistent with previously published literature and highlight potential burdens of CAR-T. In addition, the treatment landscape for CRS is changing; SUBJ with grade 1 CRS often received treatment. These data will inform the design of future studies aimed at preventing and treating CAR-T toxicities. [Table: see text]
Mammography in women with sickle cell disease.
Authors: Marwah Wafa Farooqui, Faiz Hussain, Xu Zhang, Rayyan Haqqani, Kaitlin Sung, Santosh L. Saraf
Journal: Journal of Clinical Oncology (2023)

e22509 Background: Sickle cell disease (SCD) is an inherited blood disorder affecting 100,000 people in the US with a median life expectancy of 54 years. As this population ages, it is important to focus on wellness screenings. Literature review has mixed results on the prevalence of malignancies in SCD. Initiation of BC screening is recommended between age 40-50. Patients with SCD have risk factors for breast cancer (BC) including radiation exposure, nulliparity/decreased parity, dense breasts, African American race, lack of physical activity, and use of allogenic Hematopoietic Stem Cell Transplant with total body irradiation and alkylating agent conditioning regimens. This study's purpose is to determine if these patients are being adequately screened and if guidelines for the general population are appropriate for SCD patients given their potential increased risk. Methods: This is a single center retrospective study of women with SCD who are &gt;40 with an encounter between 2018-2022. Data collection included: screening age, recent mammogram date, American College of Radiology (ACR) category for breast density (BD), family history of cancer, type of SCD, menopausal status, and Body Mass Index (BMI). Ordinal logistical regression model was used for statistical analysis. Results: A total of 156 patients were identified and 71% screened for BC; however only 56% had screening in the last 2 years. With a binomial test, the difference between CDC 2019 African American women and SCD regarding screen is not significant (P=1). The average age for screening was 44. Over half of our patients (53%) have dense breasts. Younger age at screen and lower BMI are both related to a higher density score (Table). Conclusions: As per guidelines, breast awareness (age 25) and mammography (age 40) should be offered to ensure early detection in the general population. The question arises if there should be earlier screening with an alternative imaging modality in SCD patients given increased breast density, potential risk factors, and lower life expectancy. However, it is important to consider the risks versus benefits of early screening. Screening can provide better outcomes, as SCD patients might not tolerate standard treatments for advanced disease. Our findings present a new challenge regarding BD. Increased BD decreases the accuracy of mammograms and requires additional imaging. Higher BD is found in younger women with lower BMI, but here fertility may be an additional factor as it differs in patients with SCD. The limitation of our study is that it is a retrospective, single institution study during a pandemic. Future studies are needed to closely examine if SCD patients are at increased risk given density findings and if there is a need for earlier or alternative modality of screening other than mammography. [Table: see text]
Immune features of ovarian tumors with a good response to neo-adjuvant chemotherapy in combination with an anti-PD-L1 alone or with an anti-CTLA4: Data from the randomized IneOV trial (a GINECO study).
Authors: Alexandra Leary, Laure Chardin, Catherine Genestie, Alain Lortholary, Jerome Alexandre, Thibault De La Motte Rouge, Veronique D'hondt, Anne Floquet, Aude-Marie Savoye, Nicolas Delanoy, Céline Gavoille, Benoit You, Julien Grenier, Elisa Yaniz-Galende
Journal: Journal of Clinical Oncology (2023)

5586 Background: We have shown that chemotherapy may have immunomodulatory properties and prime the tumor microenvironment (TME) by recruiting cytotoxic immune cells. We previously reported that neoadjuvant chemotherapy (NACT) associated with Durvalumab (D) +/- Tremelimumab (T) resulted in encouraging complete resection (70%) and complete pathological response (18%) rates in patients with unresectable ovarian cancer. Here, we aimed to 1) characterize the immune TME at baseline of responders compared to non-responders and 2) describe changes in immune TME in paired tumor samples at diagnosis and after 3 cycles of NACT with D +/- T in the randomized IneOV trial. Methods: Tumor samples from IneOV trial (55 at diagnosis, 40 after treatment) were analyzed for CD3+, CD68+ and CD20+ by multiplexed immunohistochemistry. Stromal and intra-epithelial TILs were scored as percentage of positive surface. Patients were classified as good pathological responders (pR) (CRS3) or pathological non-responders (pNR) (CRS1 or 2). Intra-tumoral T cell infiltration was described as High or Low (intraepithelial (ie)CD3+ &gt; median vs &lt; , respectively). Non parametric statistical tests were used. We evaluated the correlation of the markers with each others (Spearman test) and with pathological response rate (Mann-Withney test). Results: At diagnosis, in the intra-epithelial compartment of the TME, the most abundant cells were macrophages (median ieCD68+ = 3,4) compared to T (ieCD3+ = 1.1), B (ieCD20+ ND) ANOVA p-value = 0.002 and &lt; 0.0001 respectively . In individual tumors, infiltration by the 3 different immune subsets was poorly correlated suggesting immune TME heterogeneity in OC. Pathological response was evaluable in 64 patients: 19 pR and 45 pNR. At diagnosis, CD3+ (p = 0.02) and CD68+ (p = 0.006) infiltration was significantly higher in pR tumors compared to pNR. Most of pR (76%) had high intra-tumoral CD3+ infiltration versus 39% in pNR (p = 0.011). After treatment, tumors with pR showed significantly greater CD3+ intra-epithelial infiltration compared to pNR (p = 0.047). Conclusions: Our results suggest that good pathological response to NACT +D+/-T is associated with high levels of both T cells and macrophages in iTME at baseline, and increased intratumoral T cell infiltration post-treatment. Work is ongoing to further characterize the iTME, especially in pNR to identify other strategies to enhance the anti-tumor immune response. Clinical trial information: NCT03249142 .
CT based radiomics signature for phenotyping histopathological subtype in patients with non-small cell lung cancer.
Authors: Yan Liu, Fadila Zerka, Sylvain Bodard, Mehdi Felfli, Charles Voyton, Alexandre Thinnes, Sebastien Jacques, Antoine Iannessi
Journal: Journal of Clinical Oncology (2023)

e20599 Background: The determination of the histopathology of non-small cell lung cancer (NSCLC) is crucial for guiding the appropriate therapeutic strategy, affecting prognosis and recurrence rates. In addition, targetable oncologic mutations are highly correlated to histological subtypes. Conventional methods such as biopsy or surgical excision are the primary methods for histology determination but are invasive, costly, and have limitations such as sampling error. Computed tomography (CT) scans, widely used for NSCLC diagnosis and follow-up, offer a non-invasive alternative through radiomics-based models that provide comprehensive analysis of the entire tumor and surrounding tissue, improving patient selection and stratification in clinical trials and enhancing the development of molecularly targeted drugs. The goal of this study was to evaluate the ability of a CT-based radiomics model to predict the subtype histopathology of NSCLC patients. Methods: A total of 678 patients with advanced-stage NSCLC with at least one measurable lung lesion (≥10mm) were selected from multicenter institutions; 531 were used for training and 147 for independent testing. The test set originates from centers unique from the training cohort. Semi-automatic segmentation of the lung lesions was performed and the segmentations were retrospectively reviewed by an experienced radiologist with &gt; 20 years of experience. A total of 1246 radiomics features were extracted using the Pyradiomics package. Ten Robust features were selected first by removing all features with variances near zero, then by applying Maximum Relevance — Minimum Redundancy to the remaining features. All selected features were standardized before modeling. A support vector machines classifier was trained using a five-fold cross-validation and Random Over-Sampling Examples to classify the histology of NSCLC patients (Squamous vs. Non-Squamous). Results: The model trained with the radiomics features achieved a mean area under the curve (AUC) of 0.80 (95% CI, ±0.05) on the cross-validation and an AUC of 0.77 (95% CI, ±0.05) on the test set. Conclusions: Results showed that the model was able to accurately classify the histology of NSCLC patients as squamous vs. non-squamous in a multicenter setting. It highlights the promise of CT-based radiomics in determining the histopathology or other molecular biomarkers of NSCLC, offering a more efficient, cost-effective, and less invasive alternative to traditional tissue analysis methods. Our findings suggest that this non-invasive method has the potential to improve patient selection and stratification and enhance the development of molecularly targeted drugs. These results underscore the importance of incorporating advanced imaging techniques and machine learning algorithms into oncology practice for better patient outcomes.
Correlations between overall response rate, progression-free survival and overall survival in refractory small cell lung cancer treated with lurbinectedin.
Authors: Mustafa Wasifuddin, Nosakhare Paul Ilerhunmwuwa, Narek Hakobyan, Muhammad Tahir, Hesham Abowali, Boris Avezbakiyev
Journal: Journal of Clinical Oncology (2023)

e20623 Background: Lurbinectedin is a novel second-line option for refractory small-cell lung cancer. It is a synthetic alkaloid that functions by covalently binding to DNA and generates double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. It is yet to be well established in the literature if the overall response rate (ORR) can predict progression-free survival (PFS) and/or overall survival (OS). This study aims to investigate the correlations between PFS, ORR, and OS in refractory small-cell lung cancer treated with lurbinectedin. Methods: PubMed, Google Scholar, and Clinicaltrials.gov databases were queried for randomized, phase 3 clinical trials, phase 2 trials, phase 1 trials with expansion cohorts, and retrospective and prospective studies. The criteria for eligibility included a clinical diagnosis of treatment-refractory small cell lung cancer, at least one prior line of therapy, articles in English, and lurbinectedin treatment. ORR, OS, and PFS data were extracted manually from the selected studies, and correlation analyses with Spearman’s rank correlation were performed. Results: Seventy-one articles and trials were identified. Seven articles, including 849 patients, met our criteria and were included for further analyses. OS and PFS were strongly correlated (rs = 0.9196, p-value = 0.02), whereas the correlation between OS and ORR was not statistically significant (rs = 0.6696, p-value = 0.20). Also, the correlation between ORR and PFS was not statistically significant (rS = 0.6785, p-value = 0.05419). Conclusions: There was a strong correlation between OS and PFS in studies investigating lurbinectedin use in patients with refractory small-cell lung cancer. There were no significant correlations between ORR and PFS/OS. We propose that PFS can be used as a surrogate for OS in studies involving lurbinectedin-treated refractory small-cell lung cancer, especially when the time to reach OS is protracted.
Triplet maintenance (olaparib, pembrolizumab, and bevacizumab) in <i>BRCA</i> non-mutated patients with platinum-sensitive recurrent ovarian cancer: A multi-center, single-arm phase II study (OPEB-01).
Authors: Yoo Na Kim, Boram Park, Je-Gun Joung, Jae-Weon Kim, Byoung-Gie Kim, Sang Wun Kim, Hee Seung Kim, Chel Hun Choi, Myong Cheol Lim, Natalie Yl Ngoi, David Shao Peng Tan, Jung-Yun Lee
Journal: Journal of Clinical Oncology (2023)

5584 Background: The optimal treatment of BRCA 1/2 non-mutated patients with platinum-sensitive recurrent ovarian cancer remains unknown. In this study, we evaluated the efficacy and safety of triplet maintenance therapy in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA 1/2 non-mutated patients with platinum-sensitive recurrent epithelial ovarian cancer, showing a complete/partial response after second-line platinum-based chemotherapy, were eligible. Triplet maintenance therapy (olaparib, bevacizumab, and pembrolizumab) was administered until disease progression or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at six months after therapy initiation. The secondary endpoints were PFS, overall survival, and safety. The translational objectives included biomarker evaluation with respect to survival outcomes. Results: Forty-four patients were enrolled (median age 61 years), majority with high-grade serous carcinoma (93.2%) and partial response (75.0%) to second-line chemotherapy. Overall, 54.6% were homologous recombination deficiency (HRD)-positive (genomic instability score ≥ 42) and 63.6% had PD-L1 positive tumors (combined positive score [CPS] ≥ 1). At 6 months, the PFS rate was 88.6% (95% confidence interval [CI] 75.4–96.2). The median PFS has not been reached. The most common ≥ grade 3 treatment-related adverse events (AEs) were anemia (20.5%) and neutropenia (6.8%), but there were no grade 4 AEs. Exploratory analysis demonstrated remarkable survival outcomes regardless of HRD status, whereas patients with PD-L1 CPS ≥ 1 showed improved PFS compared to those with PD-L1 CPS &lt; 1 ( P = 0·032). Analysis of molecular consensus subtype of the pre-treatment tissue samples showed that patients with mesenchymal subtype demonstrated poor PFS, compared to non-mesenchymal subtypes (p = 0.0023). Conclusions: This is the first report on triplet maintenance therapy in BRCA non-mutated platinum-sensitive recurrent ovarian cancer. The results show that the triplet maintenance therapy is efficacious with manageable toxicity, showing a particular promise for patients with molecular consensus subtype other than mesenchymal. Clinical trial information: NCT04361370 .
Safety and efficacy of inetetamab in combination with pyrotinib in HER2 mutant patients with non-small cell lung cancer (NSCLC): An open-label, phase Ib trial.
Authors: Wenfeng Fang, Yuanyuan Zhao, Yan Huang, Yaxiong Zhang, Shaodong Hong, Yihua Huang, Hongyun Zhao, Yunpeng Yang, Shen Zhao, Gang Chen, Huaqiang Zhou, Yuxiang Ma, Ningning Zhou, Li Zhang
Journal: Journal of Clinical Oncology (2023)

9105 Background: Currently, limited targeted therapies are available for HER2 mutant NSCLC patients. Previous studies have shown the antitumor activity of pyrotinib in advanced NSCLC patients with HER2 mutations. Inetetamab is a recombinant humanized anti-HER2 monoclonal antibody. Whether inetetamab combined with pyrotinib could show manageable safety and more active antitumor activity remains unknown. This study was designed to evaluate the safety and efficacy of inetetamab in combination with pyrotinib in HER2 mutant patients with advanced NSCLC. Methods: This study was an open-label, phase Ib study. The HER2 mutant patients with locally advanced or metastatic NSCLC were assigned to receive inetetamab combined with pyrotinib. The study consisted of dose-escalation part and dose-expansion part. During dose-escalation period, the parallel "3+3" dose-escalation design was used to determine the dose-limiting toxicity (DLT). Inetetamab was administered every 3 weeks (8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles) with pyrotinib (dose-escalation part, 240mg QD, 320mg QD; dose-expansion part, 320mg QD). Primary endpoint of the study was DLT dosage and safety. The DLT was assessed during the 21-day DLT evaluation period after the first dose. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression free survival and overall survival. Results: Between August 6, 2021, and August 25, 2022, 48 patients were enrolled. No DLT occurred during pyrotinib 240mg and 320mg escalation period. Therefore, pyrotinib 320mg was chosen as expansion dose. The most common treatment-related adverse events (TRAEs) were diarrhea (66.7% [2/3] in pyrotinib 240mg group, 95.6% [43/45] in pyrotinib 320mg group), rash (66.7% [2/3] in pyrotinib 240mg group, 22.2% [10/45] in pyrotinib 320mg group) and vomiting (0 in pyrotinib 240mg group, 24.4% [11/45] in pyrotinib 320mg group). TRAEs were generally Grade (G) 1-2. Only 7 patients reported G3 TRAE (1 in pyrotinib 240mg group, 6 in pyrotinib 320mg group). The preliminary efficacy was shown in the table below. The ORR and DCR of group receiving inetetamab with pyrotinib 240mg were 0% and 66.7%, respectively. The ORR and DCR of inetetamab with pyrotinib 320mg group were 36.6% and 85.4% respectively. The relationship between different mutation subtypes or co-mutations and efficacy will be updated during the conference reports. Conclusions: The preliminary data of inetetamab in combination with pyrotinib showed manageable safety and compelling antitumor activity in advanced NSCLC patients harboring HER2 mutations. Clinical trial information: NCT05016544 . [Table: see text]
Re-irradiation for recurrent head and neck cancer: Freedom from cancer recurrence rate.
Authors: Issa Mohamad, Taher Abu Hejleh, Sania Abdelqader, Lina Wahbeh, Ayat Taqash, Abdelatif Al-Mousa, Ebrahim Mayta, Akram Al-Ibraheem, Fawzi Abuhijla, Ramiz Abu Hijlih, Tariq Hussein, Wisam Al-Gargaz, Hamza Ghatasheh, Ali Hosni
Journal: Journal of Clinical Oncology (2023)

e18077 Background: Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. Methods: A retrospective analysis was performed on patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3≥ late toxicities. Results: A total of 49 cases [nasopharygeal (n = 12); laryngeal (n = 12); oral cavity (n = 11); salivary gland (n = 9); and skin (n = 5)] were identified, adjuvant or definitive rRT were delivered to 22 and 27 patients, respectively. Various rRT fractionation schedules were used and 35/49 (71%) of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year OS, DFS, LF, RF, and DM and FCRR were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs 0) and age &gt; 52 years were predictive of worse OS. While, poor PS (1-2 vs 0) and total dose of rRT &lt; 60Gy were predictive of worse DFS. Late RTOG toxicity of grade 3≥ was reported in 9(18.3%) patients. Conclusions: FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important new endpoint to be included in the rRT studies. rRT for rHNC at our cohort was successful; with a manageable level of late sever toxicity.
Supporting a climate of belonging: Justice, equity, diversity, and inclusion (B-JEDI) at the Sidney Kimmel Cancer Center (NCI-designated).
Authors: Ana Maria Lopez, Christiane El Khoury, Andrew E. Chapman
Journal: Journal of Clinical Oncology (2023)

e18626 Background: Diversity fuels discovery and is, thus, essential to the well-being of a cancer center and its members. To implement our efforts, the Sidney Kimmel Cancer Center (SKCC) appointed an Associate Director for Diversity, Equity, and Inclusion (DEI) who welcomed interested faculty, staff, and trainees to gather to consider principles, coordination, aims, and priorities to achieve Center priorities for diversity, equity, and inclusion. Methods: After an initial town-hall type gathering, an analysis of approaches at peer institutions, and subsequent subgroup incubator meetings that engaged the Associate Directors for Cancer Research Training and Education Coordination and Community Outreach and Engagement and the SKCC Scientific Programs, additional members became involved, missing potential strategic partners were identified and invited to participate, and a workplan was developed. Results: Through our inclusive process, the SKCC community affirmed equity as a cornerstone value, identified a climate that supports belonging and pathways to success as strategic priorities, and committed to disseminating a survey to guide progress towards the priorities. Our group, initially known as the DEI Committee selected as its name, Belonging-Justice, Equity, Diversity, and Inclusion (B-JEDI), and invited everyone to “B-JEDI”, acknowledging that to succeed, we must all be working towards our ideals. The B-JEDI strategic planning subgroup drafted, tested, and disseminated the survey to yield a strategic plan; and another subgroup developed a DEI mission statement for SKCC. Incubator subgroups composed of faculty, staff, trainees interested in the topic (Investigation, Awareness and Education, Health Care Delivery, Community Outreach Partnership &amp; Engagement (COPE), and Advocacy) are actively working with institutional partners to advance strategic goals and priorities. Conclusions: B-JEDI (Belonging-Justice, Equity, Diversity, and Inclusion) provides guidance and fuel to SKCC in its mission to improve lives through discovery. Composed of interested members of the SKCC community, B-JEDI is welcoming to all, has strategically engaged institutional leadership partners, and is developing processes to engage our catchment community at large. [Table: see text]